The newly reported structure of serum albumin and the recent detection of a precursor form of albumin provide much of the impetus for the proposed investigation of function and metabolism of this major serum protein. The precursor, proalbumin, has an amino-terminal peptide extension the role of which has evoked much speculation. We propose to investigate the biosynthesis of albumin, its ligand-binding functions in the circulation and its metabolic fate. To this end we will study the properties of proalbumin, its cleavage to form albumin, whether products of incomplete cleavage appear in the circulation and whether the cleaved peptide affects the rate of albumin synthesis or secretion. Similarly we still test for recognizable fragments of albumin in blood and tissues which point to the mechanism of its degradation. Testing will be performed in the rat under normal and pathological conditions and will be extended to the human wherever feasible. The possibility that altered forms of human albumin in the circulation are a cause of autoimmune disease will be explored. As isolation procedures we will use immunoabsorbents prepare with pure antibodies, affinity chromatography with recognized ligands for albumin and classical fractionation methods. To identify and characterize albumin fragments and proalbumin we will measure ligand binding and immunochemical reactivity on a micro scale following electrophoretic separation, amino acid and sequence analysis, peptide mapping, circular dichroism and gel electrophoresis. We will use these same techniques in studies aimed at detecting albumin-like molecules in lower forms of life in order to learn the original function of albumin as a circulating protein.